MicroRNA-155 contributes to shear-resistant leukocyte adhesion to human brain endothelium in vitro

Camilla Cerutti, Patricia Soblechero-Martin, Dongsheng Wu, Miguel Alejandro Lopez-Ramirez, Helga de Vries, Basil Sharrack, David Kingsley Male, Ignacio Andres Romero

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

BACKGROUND: Increased leukocyte adhesion to brain endothelial cells forming the blood-brain barrier (BBB) precedes extravasation into the central nervous system (CNS) in neuroinflammatory diseases such as multiple sclerosis (MS). Previously, we reported that microRNA-155 (miR-155) is up-regulated in MS and by inflammatory cytokines in human brain endothelium, with consequent modulation of endothelial paracellular permeability. Here, we investigated the role of endothelial miR-155 in leukocyte adhesion to the human cerebral microvascular endothelial cell line, hCMEC/D3, under shear forces mimicking blood flow in vivo.

RESULTS: Using a gain- and loss-of-function approach, we show that miR-155 up-regulation increases leukocyte firm adhesion of both monocyte and T cells to hCMEC/D3 cells. Inhibition of endogenous endothelial miR-155 reduced monocytic and T cell firm adhesion to naïve and cytokines-induced human brain endothelium. Furthermore, this effect is partially associated with modulation of the endothelial cell adhesion molecules VCAM1 and ICAM1 by miR-155.

CONCLUSIONS: Our results suggest that endothelial miR-155 contribute to the regulation of leukocyte adhesion at the inflamed BBB. Taken together with previous observations, brain endothelial miR-155 may constitute a potential molecular target for treatment of neuroinflammation diseases.

Original languageEnglish
Article number8
Number of pages7
JournalFluids and Barriers of the CNS
Volume13
DOIs
Publication statusPublished - 31 May 2016

Keywords

  • Blood-Brain Barrier/metabolism
  • Cell Adhesion/physiology
  • Cell Line
  • Cerebrovascular Circulation/physiology
  • Endothelial Cells/metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Intercellular Adhesion Molecule-1/metabolism
  • Jurkat Cells
  • MicroRNAs/antagonists & inhibitors
  • Models, Cardiovascular
  • Models, Neurological
  • Monocytes/metabolism
  • Neuroimmunomodulation/physiology
  • Shear Strength/physiology
  • T-Lymphocytes/metabolism
  • Transfection
  • Vascular Cell Adhesion Molecule-1/metabolism

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